Osteonecrosis of the femoral head (ONFH) frequently occurs after glucocorticoid (GC) treatment. Extracellular vesicles (EVs) are important nano-sized paracrine mediators of intercellular crosstalk. This study aimed to determine whether EVs from human urine-derived stem cells (USC-EVs) could protect against GC-induced ONFH and focused on the impacts of USC-EVs on angiogenesis and apoptosis to explore the mechanism by which USC-EVs attenuated GC-induced ONFH. The results in vivo showed that the intravenous administration of USC-EVs at the early stage of GC exposure could rescue angiogenesis impairment, reduce apoptosis of trabecular bone and marrow cells, prevent trabecular bone destruction and improve bone microarchitecture in the femoral heads of rats. In vitro, USC-EVs reversed the GC-induced suppression of endothelial angiogenesis and activation of apoptosis. Deleted in malignant brain tumors 1 (DMBT1) and tissue inhibitor of metalloproteinases 1 (TIMP1) proteins were enriched in USC-EVs and essential for the USC-EVs-induced pro-angiogenic and anti-apoptotic effects in GC-treated cells, respectively. Knockdown of TIMP1 attenuated the protective effects of USC-EVs against GC-induced ONFH. Our study suggests that USC-EVs are a promising nano-sized agent for the prevention of GC-induced ONFH by delivering pro-angiogenic DMBT1 and anti-apoptotic TIMP1.The rational design and controllable synthesis of functional silica-based materials have gained increased interest in a variety of biomedical and biotechnological applications due to their unique properties. The current review shows that marine organisms, such as siliceous sponges and diatoms, could be the inspiration for the fabrication of advanced biohybrid materials. Several biomolecules were involved in the molecular mechanism of biosilicification in vivo. Mimicking their behavior, functional silica-based biomaterials have been generated via biomimetic and bioinspired silicification in vitro. Additionally, several advanced technologies were developed for in vitro and in vivo immobilization of biomolecules with potential applications in biocatalysis, biosensors, bioimaging, and immunoassays. A thin silica layer could coat a single living cell or virus as a protective shell offering new opportunities in biotechnology and nanomedicine fields. Promising nanotechnologies have been developed for drug encapsulation and delivery in a targeted and controlled manner, in particular for poorly soluble hydrophobic drugs. Moreover, biomimetic silica, as a morphogenetically active biocompatible material, has been utilized in the field of bone regeneration and in the development of biomedical implantable devices.In Ontario, on March 16th, 2020, a directive was issued to all acute care hospitals to halt non-essential procedures in anticipation for a potential surge in COVID-19 patients. This included scheduled outpatient cardiac surgical and interventional procedures that required the use of intensive care units, ventilators, and skilled critical care personnel, given that these procedures would draw from the same pool of resources required for critically ill COVID-19 patients. We adapted the COVID-19 Resource Estimator (CORE) decision analytic model by adding a cardiac component to determine the impact of various policy decisions on the incremental waitlist growth and estimated waitlist mortality for three key groups of cardiovascular disease patients; coronary artery disease, valvular heart disease, and arrhythmias. We provided predictions based on COVID-19 epidemiology available in real-time, in 3 phases. First, in the initial crisis phase, in a worst case scenario, we showed that the potential number of waitlist related cardiac deaths would be orders of magnitude less than those who would die of COVID-19 if critical cardiac care resources were diverted to the care of COVID-19 patients. Second, with better local epidemiology data, we predicted that across five regions of Ontario, there may be insufficient resources to resume all elective outpatient cardiac procedures. Finally in the recovery phase, we showed that the estimated incremental growth in waitlist for all cardiac procedures is likely substantial. These outputs informed timely, data-driven decisions during the COVID-19 pandemic regarding the provision of cardiovascular care.Background Perampanel (PER) is a novel antiepileptic drug approved as an add-on therapy for focal onset seizures with or without generalization and primary generalized tonic-clonic seizures. Aim of this study was to evaluate PER efficacy and tolerability as add-on therapy in patients with drug-resistant focal onset seizures and especially temporal lobe epilepsy (TLE). Methods An observational, prospective, multicentre study on adult with drug-resistant focal epilepsy consecutively recruited from six Italian tertiary epilepsy centres. All patients received add-on PER according to indication and clinical judgement. Seizure frequency and adverse events (AEs) were recorded at 6 and 12 months after PER introduction. Results Study sample comprised 246 patients, 77 of which with TLE. Seventy-five (35.9%) out of 209 and 66 (38.8%) out of 170 patients still taking PER resulted to be responders (i.e. ?50% of seizure frequency or seizure free) after six and 12 months, respectively. In the TLE group, 39 (57.3%) out of 68 subjects on PER after 6 months and 32 (60.4%) out of 53 subjects taking PER after 12 months were responders. Overall reported incidence of AEs was 26.1%. In 28 cases (11.3%) AEs lead/contributed to PER discontinuation. The most frequently reported AE were dizziness (14/84) and somnolence (14/84). Regarding TLE patients, 25.9% of them experienced at least one AE and discontinuation for AEs occurred in eight (10.4%). Conclusions This study confirmed the good efficacy and safety of PER for drug-resistant focal epilepsy in real-life conditions and, above all, for the first time provide its effectiveness in patients with TLE.Inflammation is a tightly regulated process. During the past decade it has become clear that the resolution of inflammation is an active process and its dysregulation can contribute to chronic inflammation. Several cells and soluble mediators, including lipid mediators, regulate the course of inflammation and its resolution. It is, however, unclear which signals and cells are involved in initiating the resolution process. Macrophages are tissue resident cells and key players in regulating tissue inflammation through secretion of soluble mediators, including lipids. We hypothesize that persistent inflammatory stimuli can initiate resolution pathways in macrophages. In this study, we detected 21 lipids in LPS-stimulated human monocyte-derived macrophages by liquid chromatography coupled to tandem mass spectrometry. https://www.selleckchem.com/btk.html Cyclooxygenase-derived Prostaglandins were observed in the first six hours of stimulation. Interestingly, a switch towards 15-lipoxygenase products, such as the pro-resolving lipid precursors 15-HEPE and 17-HDHA was observed after 24 h.